US2007232615A1PendingUtilityA1
Chemical Compounds
Est. expirySep 2, 2024(expired)· nominal 20-yr term from priority
A61P 9/14A61P 7/06A61P 43/00A61P 7/00A61P 37/02A61P 37/08A61P 3/10A61P 37/06A61P 31/12A61P 31/04A61P 35/02A61P 31/18A61P 31/00A61P 35/00A61P 29/00A61P 25/28A61P 27/16A61P 11/08A61P 19/02A61P 19/00A61P 21/00A61P 11/00A61P 17/00A61P 17/02A61P 17/06A61P 13/12A61P 17/08A61P 1/04A61P 21/04A61P 11/06A61P 1/00A61P 17/04C07D 471/04A61K 31/437
45
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Claims
Abstract
The present invention provides novel compounds that demonstrate protective effects on target cells from HIV infection in a manner as to bind to a chemokine receptor, and which affect the binding of the natural ligand or chemokine to a receptor such as CXCR4 of a target cell.
Claims
exact text as granted — not AI-modified1 . A compound of formula (I):
wherein:
t is 0, 1, or 2;
each R independently is H, alkyl, alkenyl, alkynyl, haloalkyl, cycloalkyl, —R a Ay, —R a OR 10 , or —R a S(O) q R 10 ;
each R 1 independently is halogen, haloalkyl, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, -Ay, —NHAy, -Het, —NHHet, —OR 10 , —OAy, —OHet, —R a OR 10 , —NR 6 R 7 , —R a NR 6 R 7 , —R a C(O)R 10 , —C(O)R 10 , —CO 2 R 10 , —R a CO 2 R 10 , —C(O)NR 6 R 7 , —C(O)Ay, —C(O)Het, —S(O) 2 NR 6 R 7 , —S(O) q R 10 , —S(O) q Ay, cyano, nitro, or azido;
n is 0, 1, or 2;
R 2 is selected from a group consisting of H, alkyl, haloalkyl, cycloalkyl, R a cycloalkyl alkenyl, alkynyl, —R a Ay, —R a OR 5 , or —R a S(O) q R 5 ; wherein R 2 is not substituted with amine or alkylamine;
R 3 is H, alkyl, haloalkyl, cycloalkyl, alkenyl, alkynyl, —R a Ay, or —R a S(O) q R 5 ; each R 4 independently is halogen, haloalkyl, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, -Ay, —NHAy, -Het, —NHHet, —OR 10 , —OAy, —OHet, —R a OR 10 , —NR 6 R 7 , R a NR 6 R 7 , —R a C(O)R 10 , —C(O)R 10 , —CO 2 R 10 , —R a CO 2 R 10 , —C(O)NR 6 R 7 , —C(O)Ay, —C(O)Het, —S(O) 2 NR 6 R 7 , —S(O) q R 10 , —S(O) q Ay, cyano, nitro, or azido;
m is 0, 1, or 2;
each R 5 independently is H, alkyl, alkenyl, alkynyl, cycloalkyl, or -Ay;
p is 0 or 1;
Y is —NR 10 —, —O—, —C(O)NR 10 —, —NR 10 C(O)—, —C(O)O—, —C(O)O—, —NR 10 C(O)N(R 10 )—, —S(O) q —, —S(O) q NR 10 —, or —NR 10 S(O) q —;
X is —N(R 10 ) 2 , —R a N(R 10 ) 2 , -AyN(R 10 ) 2 , —R a AyN(R 10 ) 2 , -AyR a N(R 10 ) 2 , —R a AyR a N(R 10 ) 2 , -Het, —R a Het, -HetN(R 10 ) 2 , —R a HetN(R 10 ) 2 , -HetR a N(R 10 ) 2 , —R a HetR a N(R 10 ) 2 , -HetR a Ay, or -HetR a Het;
each R a independently is alkylene optionally substituted with one or more of alkyl, oxo or hydroxyl, cycloalkylene optionally substituted with one or more of alkyl, oxo or hydroxyl, alkenylene, cycloalkenylene, or alkynylene;
each R 10 independently is H, alkyl, cycloalkyl, alkenyl, alkynyl, cycloalkenyl, —R a cycloalkyl, —R a OH, —R a OR 5 , —R a NR 6 R 7 , or —R a Het;
each of R 6 and R 7 independently are selected from H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, —R a cycloalkyl, —R a OH, —R a OR 5 , —R a NR 8 R 9 , -Ay, -Het, —R a Ay, —R a Het, or —S(O) q R 5 ;
each of R 8 and R 9 independently are selected from H or alkyl;
each q independently is 0, 1, or 2;
each Ay independently represents an optionally substituted aryl group; and
each Het independently represents an optionally substituted 4-, 5-, or 6-membered heterocyclyl or heteroaryl group; or a pharmaceutically acceptable salt or ester thereof.
2 . The compound of claim 1 wherein -Het is optionally substituted with at least one of alkyl, alkoxy, hydroxyl, halogen, haloalkyl, cycloalkyl, cycloalkoxy, cyano, amide, amino, or alkylamino.
3 . The compound of claim 1 wherein -Ay is optionally substituted with at least one of alkyl, alkoxy, hydroxyl, halogen, haloalkyl, cycloalkyl, cycloalkoxy, cyano, amide, amino, or alkylamino.
4 . The compound of claim 1 wherein t is 1.
5 . The compound of claim 1 wherein t is 2.
6 . The compound of claim 1 wherein R is H, alkyl, cycloalkyl, or R a OR 10 .
7 . (canceled)
8 . (canceled)
9 . The compound of claim 1 wherein n is 0.
10 . The compound of claim 1 wherein n is 1 and R 1 is halogen, haloalkyl, alkyl, OR 10 , NR 6 R 7 , CO 2 R 10 , CONR 6 R 7 , or cyano.
11 . The compound of claim 1 wherein R 2 is H, alkyl, haloalkyl, R a OR 5 or cycloalkyl.
12 . The compound of claim 1 wherein R 2 is R a Ay or R a cycloalkyl.
13 . The compound of claim 11 wherein R 2 is H, alkyl, or cycloalkyl.
14 . (canceled)
15 . The compound of claim 1 wherein R 3 is H, alkyl, haloalkyl, cycloalkyl, alkenyl, or alkynyl.
16 . The compound of claim 15 wherein R 3 is H, alkyl, haloalkyl, or cycloalkyl.
17 . (canceled)
18 . (canceled)
19 . The compound of claim 1 wherein m is 0.
20 . (canceled)
21 . The compound of claim 20 wherein m is 1.
22 . The compound of claim 21 wherein R 4 is halogen, haloalkyl, alkyl, OR 10 , NR 6 R 7 , CO 2 R 10 , CONR 6 R 7 , or cyano.
23 . The compound of claim 1 wherein p is 0 and X is —R a N(R 10 ) 2 , -AyR a N(R 10 ) 2 , —R a AyR a N(R 10 ) 2 , -Het, —R a Het, -HetN(R 10 ) 2 , —R a HetN(R 10 ) 2 , or -HetR a N(R 10 ) 2 .
24 . The compound of claim 23 wherein X is —R a N(R 10 ) 2 , -Het, —R a Het, -HetN(R 10 ) 2 , —R a HetN(R 10 ) 2 , or -HetR a N(R 10 ) 2 .
25 . The compound of claim 24 wherein X is —R a N(R 10 ) 2 , -Het, —R a Het, or -HetN(R 10 ) 2 .
26 . The compound of claim 1 wherein
p is 1; Y is —N(R 10 )—, —O—, —S—, —C(O)NR 10 —, —NR 10 C(O)—, or —S(O) q NR 10 —; and X is —R a N(R 10 ) 2 , -AyR a N(R 10 ) 2 , —R a AyR a N(R 10 ) 2 , -Het, —R a Het, -HetN(R 10 ) 2 , —R a HetN(R 10 ) 2 , or -HetR a N(R 10 ) 2 .
27 . The compound of claim 26 wherein
Y is —N(R 10 )—, —O—, —C(O)NR 10 —, or —NR 10 C(O)—; and X is —R a N(R 10 ) 2 , -Het, —R a Het, or -HetN(R 10 ) 2 .
28 . The compound of claim 1 wherein t is 1 or 2; R is H or alkyl; R 2 is H, alkyl, or cycloalkyl; R 3 is H, alkyl, haloalkyl, or cycloalkyl; n is 0; and m is 0.
29 . The compound of claim 28 wherein p is 0 and X is -Het or -HetN(R 10 ) 2 , R 10 is H or alkyl and Het is unsubstituted or substituted with C 1 -C 6 alkyl or C 3 -C 8 cycloalkyl.
30 . The compound of claim 28 wherein p is 1; Y is —N(R 10 )—, —O—, —CONR 10 —, or —NR 10 CO—; X is -Het or -HetN(R 10 ) 2 , and Het is unsubstituted or substituted with C 1 -C 6 alkyl or C 3 -C 8 cycloalkyl.
31 . The compound of claim 30 wherein Y is —N(R 10 )— or —O— and X is -Het.
32 . The compound of claim 1 wherein p is 0; X is -HetN(R 10 ) 2 ; and R 10 is H or alkyl.
33 . The compound of claim 1 wherein p is 1 and Y is —N(R 10 )—, —O—, —C(O)NR 10 —, or —NR 10 C(O)—; X is -Het or -HetN(R 10 ) 2 , and Het is unsubstituted or substituted with C 1 -C 6 alkyl or C 3 -C 8 cycloalkyl.
34 . The compound of claim 1 wherein the substituent —Y p —X is located on the depicted imidazopyridine ring as in formula (I′):
35 . The compound of claim 1 wherein Het is piperidine, piperazine, azetidine, pyrrolidine, imidazole, or pyridine.
36 . The compound of claim 1 wherein p is 0 and X is -Het.
37 . The compound of claim 36 wherein -Het is unsubstituted or substituted with one or more C 1 -C 6 alkyl or C 3 -C 8 cycloalkyl.
38 . A compound selected from the group consisting of
N-Methyl-N-{[5-(4-methyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-5,6,7,8-tetrahydro-8-quinolinamine; N-{[5-(4-Ethyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-N-methyl-5,6,7,8-tetrahydro-8-quinolinamine; N-Methyl-N-({5-[4-(1-methylethyl)-1-piperazinyl]imidazo[1,2-a]pyridin-2-yl}methyl)-5,6,7,8-tetrahydro-8-quinolinamine; N-Methyl-N-{[5-(1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-5,6,7,8-tetrahydro-8-quinolinamine; N,N,N′-Trimethyl-N′-(2-{[methyl(5,6,7,8-tetrahydro-8-quinolinyl)amino]methyl}imidazo[1,2-a]pyridin-5-yl)-1,2-ethanediamine; N-{[5-(3,5-Dimethyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-N-methyl-5,6,7,8-tetrahydro-8-quinolinamine; N-Methyl-N-{[5-(3,4,5-trimethyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-5,6,7,8-tetrahydro-8-quinolinamine; N-(1-Methylethyl)-N-{[5-(4-methyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-5,6,7,8-tetrahydro-8-quinolinamine; N-(1-Methylethyl)-N-({5-[4-(1-methylethyl)-1-piperazinyl]imidazo[1,2-a]pyridin-2-yl}methyl)-5,6,7,8-tetrahydro-8-quinolinamine; N-[(5-{4-[(Dimethylamino)methyl]phenyl}imidazo[1,2-a]pyridin-2-yl)methyl]-N-methyl-5,6,7,8-tetrahydro-8-quinolinamine; N-(1-Methylethyl)-N-{[5-(1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-5,6,7,8-tetrahydro-8-quinolinamine; N-({5-[(3R)-3-(Dimethylamino)-1-pyrrolidinyl]imidazo[1,2-a]pyridin-2-yl}methyl)-N-methyl-5,6,7,8-tetrahydro-8-quinolinamine; N-({5-[(3S)-3-(Dimethylamino)-1-pyrrolidinyl]imidazo[1,2-a]pyridin-2-yl}methyl)-N-methyl-5,6,7,8-tetrahydro-8-quinolinamine; N-{[5-(3-Amino-1-azetidinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-N-methyl-5,6,7,8-tetrahydro-8-quinolinamine; N-({5-[(3R)-3-Amino-1-pyrrolidinyl]imidazo[1,2-a]pyridin-2-yl}methyl)-N-methyl-5,6,7,8-tetrahydro-8-quinolinamine; N-Methyl-N-({5-[methyl(1-methyl-3-pyrrolidinyl)amino]imidazo[1,2-a]pyridin-2-yl}methyl)-5,6,7,8-tetrahydro-8-quinolinamine; N-{[5-(Hexahydro-1H-1,4-diazepin-1-yl)imidazo[1,2-a]pyridin-2-yl]methyl}-N-methyl-5,6,7,8-tetrahydro-8-quinolinamine; N-Methyl-N-{[5-(4-methylhexahydro-1H-1,4-diazepin-1-yl)imidazo[1,2-a]pyridin-2-yl]methyl}-5,6,7,8-tetrahydro-8-quinolinamine; N-Methyl-N-[(5-{4-[2-(methyloxy)ethyl]-1-piperazinyl}imidazo[1,2-a]pyridin-2-yl)methyl]-5,6,7,8-tetrahydro-8-quinolinamine; N-Cyclopropyl-N-{[5-(4-methyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-5,6,7,8-tetrahydro-8-quinolinamine; N-Methyl-N-({5-[4-(methylamino)-1-piperidinyl]imidazo[1,2-a]pyridin-2-yl}methyl)-5,6,7,8-tetrahydro-8-quinolinamine; N-{[5-(4-Amino-1-piperidinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-N-methyl-5,6,7,8-tetrahydro-8-quinolinamine; N-({5-[4-(Dimethylamino)-1-piperidinyl]imidazo[1,2-a]pyridin-2-yl}methyl)-N-methyl-5,6,7,8-tetrahydro-8-quinolinamine; N-{[5-(4-M ethyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-5,6,7,8-tetrahydro-8-quinolinamine; N-Methyl-N-{[5-(4-methyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-6,7-dihydro-5H-cyclopenta[b]pyridin-7-amine; N-Methyl-N-{[5-(4-methyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-9-amine; (8S)—N-Methyl-N-{[5-(4-methyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-5,6,7,8-tetrahydro-8-quinolinamine; (8R)—N-Methyl-N-{[5-(4-methyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-{[5-(4-Methyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-N-(2-methylpropyl)-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-Ethyl-N-{[5-(4-methyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-(1-Methylethyl)-N-{[5-(4-methyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-{[5-(4-Methyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-N-propyl-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-(Cyclopropylmethyl)-N-{[5-(4-methyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-Butyl-N-{[5-(4-methyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-{[5-(4-Methyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-N-(phenylmethyl)-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-[(2-Fluorophenyl)methyl]-N-{[5-(4-methyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-[(3-Fluorophenyl)methyl]-N-{[5-(4-methyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-[(4-Fluorophenyl)methyl]-N-{[5-(4-methyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-[(3-Bromophenyl)methyl]-N-{[5-(4-methyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-[(4-Bromophenyl)methyl]-N-{[5-(4-methyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-[(2-Methylphenyl)methyl]-N-{[5-(4-methyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-[(3-Methylphenyl)methyl]-N-{[5-(4-methyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-[(4-Methylphenyl)methyl]-N-{[5-(4-methyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-{[5-(4-Methyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-N-{[3-(trifluoromethyl)phenyl]methyl}-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-{[5-(4-Methyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-N-{[4-(trifluoromethyl)phenyl]methyl}-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-{[2-(Methyloxy)phenyl]methyl}-N-{[5-(4-methyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-{[3-(Methyloxy)phenyl]methyl}-N-{[5-(4-methyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-{[4-(Methyloxy)phenyl]methyl}-N-{[5-(4-methyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-{[4-(1-Methylethyl)phenyl]methyl}-N-{[5-(4-methyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-(4-Biphenylylmethyl)-N-{[5-(4-methyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-{[5-(4-Methyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-N-{[4-(2-methylpropyl)phenyl]methyl}-5,6,7,8-tetrahydro-8-quinolinamine; 2-{{[5-(4-Methyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}[(8S)-5,6,7,8-tetrahydro-8-quinolinyl]amino}ethanol; 3-{{[5-(4-Methyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-[(8S)-5,6,7,8-tetrahydro-8-quinolinyl]amino}-1-propanol; (8S)—N-{[5-(4-Amino-1-piperidinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-N-methyl-5,6,7,8-tetrahydro-8-quinolinamine; N,N,N′-Trimethyl-N′-[2-({methyl[(8S)-5,6,7,8-tetrahydro-8-quinolinyl]amino}methyl)imidazo[1,2-a]pyridin-5-yl]-1,2-ethanediamine; (8S)—N-{[5-(Hexahydropyrrolo[1,2-a]pyrazin-2(1H)-yl)imidazo[1,2-a]pyridin-2-yl]methyl}-N-methyl-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-({5-[(3R)-3-(Dimethylamino)-1-pyrrolidinyl]imidazo[1,2-a]pyridin-2-yl}methyl)-N-methyl-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-{[5-(Hexahydro-1H-1,4-diazepin-1-yl)imidazo[1,2-a]pyridin-2-yl]methyl}-N-methyl-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-Methyl-N-{[5-(4-methylhexahydro-1H-1,4-diazepin-1-yl)imidazo[1,2-a]pyridin-2-yl]methyl}-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-Methyl-N-({5-[methyl(1-methyl-3-pyrrolidinyl)amino]imidazo[1,2-a]pyridin-2-yl}methyl)-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-Methyl-N-({5-[methyl(1-methyl-4-piperidinyl)amino]imidazo[1,2-a]pyridin-2-yl}methyl)-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-{[5-(4-Ethyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-N-methyl-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-Methyl-N-({5-[4-(1-methylethyl)-1-piperazinyl]imidazo[1,2-a]pyridin-2-yl}methyl)-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-({5-[(3S)-3-(Dimethylamino)-1-pyrrolidinyl]imidazo[1,2-a]pyridin-2-yl}methyl)-N-methyl-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-({5-[(3R)-3-Amino-1-pyrrolidinyl]imidazo[1,2-a]pyridin-2-yl}methyl)-N-methyl-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-({5-[(3R)-3-(Diethylamino)-1-pyrrolidinyl]imidazo[1,2-a]pyridin-2-yl}methyl)-N-methyl-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-({5-[(3R)-3-(Dimethylamino)-1-pyrrolidinyl]imidazo[1,2-a]pyridin-2-yl}methyl)-N-ethyl-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-({5-[(3R)-3-(Dimethylamino)-1-pyrrolidinyl]imidazo[1,2-a]pyridin-2-yl}methyl)-N-propyl-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-({5-[(3R)-3-(Dimethylamino)-1-pyrrolidinyl]imidazo[1,2-a]pyridin-2-yl}methyl)-N-(1-methylethyl)-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-(Cyclopropylmethyl)-N-({5-[(3R)-3-(dimethylamino)-1-pyrrolidinyl]imidazo[1,2-a]pyridin-2-yl}methyl)-5,6,7,8-tetrahydro-8-quinolinamine; and (8S)—N-Methyl-N-{1-[5-(4-methyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]ethyl}-5,6,7,8-tetrahydro-8-quinolinamine; N,N-Dimethyl-N′-[2-({methyl[(8S)-5,6,7,8-tetrahydro-8-quinolinyl]amino}methyl)imidazo[1,2-a]pyridin-5-yl]-1,2-ethanediamine; (8S)—N-Methyl-N-[(5-{[2-(1-pyrrolidinyl)ethyl]amino}imidazo[1,2-a]pyridin-2-yl)methyl]-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-Methyl-N-[(5-{[2-(1-piperidinyl)ethyl]amino}imidazo[1,2-a]pyridin-2-yl)methyl]-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-[(5-{[2-(Dimethylamino)ethyl]oxy}imidazo[1,2-a]pyridin-2-yl)methyl]-N-methyl-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-Methyl-N-[(5-{[2-(1-pyrrolidinyl)ethyl]oxy}imidazo[1,2-a]pyridin-2-yl)methyl]-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-Methyl-N-[(5-{[2-(1-piperidinyl)ethyl]oxy}imidazo[1,2-a]pyridin-2-yl)methyl]-5,6,7,8-tetrahydro-8-quinolinamine; and pharmaceutically acceptable salts or esters thereof.
39 . A compound selected from the group consisting of
N-Methyl-N-{[5-(4-methyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-5,6,7,8-tetrahydro-8-quinolinamine; N-{[5-(4-Ethyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-N-methyl-5,6,7,8-tetrahydro-8-quinolinamine; N-Methyl-N-({5-[4-(1-methylethyl)-1-piperazinyl]imidazo[1,2-a]pyridin-2-yl}methyl)-5,6,7,8-tetrahydro-8-quinolinamine; N-Methyl-N-{[5-(1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-5,6,7,8-tetrahydro-8-quinolinamine; N-(1-Methylethyl)-N-{[5-(4-methyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-5,6,7,8-tetrahydro-8-quinolinamine; N-(1-Methylethyl)-N-({5-[4-(1-methylethyl)-1-piperazinyl]imidazo[1,2-a]pyridin-2-yl}methyl)-5,6,7,8-tetrahydro-8-quinolinamine; N-(1-Methylethyl)-N-{[5-(1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-5,6,7,8-tetrahydro-8-quinolinamine; N-({5-[(3R)-3-(Dimethylamino)-1-pyrrolidinyl]imidazo[1,2-a]pyridin-2-yl}methyl)-N-methyl-5,6,7,8-tetrahydro-8-quinolinamine; N-{[5-(3-Amino-1-azetidinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-N-methyl-5,6,7,8-tetrahydro-8-quinolinamine; N-({5-[(3R)-3-Amino-1-pyrrolidinyl]imidazo[1,2-a]pyridin-2-yl}methyl)-N-methyl-5,6,7,8-tetrahydro-8-quinolinamine; N-Methyl-N-({5-[methyl(1-methyl-3-pyrrolidinyl)amino]imidazo[1,2-a]pyridin-2-yl}methyl)-5,6,7,8-tetrahydro-8-quinolinamine; N-{[5-(Hexahydro-1H-1,4-diazepin-1-yl)imidazo[1,2-a]pyridin-2-yl]methyl}-N-methyl-5,6,7,8-tetrahydro-8-quinolinamine; N-Methyl-N-{[5-(4-methylhexahydro-1H-1,4-diazepin-1-yl)imidazo[1,2-a]pyridin-2-yl]methyl}-5,6,7,8-tetrahydro-8-quinolinamine; N-Methyl-N-[(5-{4-[2-(methyloxy)ethyl]-1-piperazinyl}imidazo[1,2-a]pyridin-2-yl)methyl]-5,6,7,8-tetrahydro-8-quinolinamine; N-Cyclopropyl-N-{[5-(4-methyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-5,6,7,8-tetrahydro-8-quinolinamine; N-Methyl-N-({5-[4-(methylamino)-1-piperidinyl]imidazo[1,2-a]pyridin-2-yl}methyl)-5,6,7,8-tetrahydro-8-quinolinamine; N-{[5-(4-Amino-1-piperidinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-N-methyl-5,6,7,8-tetrahydro-8-quinolinamine; N-({5-[4-(Dimethylamino)-1-piperidinyl]imidazo[1,2-a]pyridin-2-yl}methyl)-N-methyl-5,6,7,8-tetrahydro-8-quinolinamine; N-{[5-(4-Methyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-5,6,7,8-tetrahydro-8-quinolinamine; N-Methyl-N-{[5-(4-methyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-6,7-dihydro-5H-cyclopenta[b]pyridin-7-amine; N-Methyl-N-{[5-(4-methyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-9-amine; (8S)—N-Methyl-N-{[5-(4-methyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-5,6,7,8-tetrahydro-8-quinolinamine; (8R)—N-Methyl-N-{[5-(4-methyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-{[5-(4-Methyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-N-(2-methylpropyl)-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-Ethyl-N-{[5-(4-methyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-(1-Methylethyl)-N-{[5-(4-methyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-{[5-(4-Methyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-N-propyl-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-(Cyclopropylmethyl)-N-{[5-(4-methyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-Butyl-N-{[5-(4-methyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-5,6,7,8-tetrahydro-8-quinolinamine; 2-{{[5-(4-Methyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}[(8S)-5,6,7,8-tetrahydro-8-quinolinyl]amino}ethanol; 3-{{[5-(4-M ethyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}[(8S)-5,6,7,8-tetrahydro-8-quinolinyl]amino}-1-propanol; (8S)—N-{[5-(4-Amino-1-piperidinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-N-methyl-5,6,7,8-tetrahydro-8-quinolinamine; N,N,N′-Trimethyl-N′-[2-({methyl[(8S)-5,6,7,8-tetrahydro-8-quinolinyl]amino}methyl)imidazo[1,2-a]pyridin-5-yl]-1,2-ethanediamine; (8S)—N-{[5-(Hexahydropyrrolo[1,2-a]pyrazin-2(1H)-yl)imidazo[1,2-a]pyridin-2-yl]methyl}-N-methyl-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-({5-[(3R)-3-(Dimethylamino)-1-pyrrolidinyl]imidazo[1,2-a]pyridin-2-yl}methyl)-N-methyl-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-{[5-(Hexahydro-1H-1,4-diazepin-1-yl)imidazo[1,2-a]pyridin-2-yl]methyl}-N-methyl-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-Methyl-N-{[5-(4-methylhexahydro-1H-1,4-diazepin-1-yl)imidazo[1,2-a]pyridin-2-yl]methyl}-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-Methyl-N-({5-[methyl(1-methyl-3-pyrrolidinyl)amino]imidazo[1,2-a]pyridin-2-yl}methyl)-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-Methyl-N-({5-[methyl(1-methyl-4-piperidinyl)amino]imidazo[1,2-a]pyridin-2-yl}methyl)-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-{[5-(4-Ethyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-N-methyl-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-Methyl-N-({5-[4-(1-methylethyl)-1-piperazinyl]imidazo[1,2-a]pyridin-2-yl}methyl)-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-({5-[(3S)-3-(Dimethylamino)-1-pyrrolidinyl]imidazo[1,2-a]pyridin-2-yl}methyl)-N-methyl-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-({5-[(3R)-3-Amino-1-pyrrolidinyl]imidazo[1,2-a]pyridin-2-yl}methyl)-N-methyl-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-({5-[(3R)-3-(Diethylamino)-1-pyrrolidinyl]imidazo[1,2-a]pyridin-2-yl}methyl)-N-methyl-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-({5-[(3R)-3-(Dimethylamino)-1-pyrrolidinyl]imidazo[1,2-a]pyridin-2-yl}methyl)-N-ethyl-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-({5-[(3R)-3-(Dimethylamino)-1-pyrrolidinyl]imidazo[1,2-a]pyridin-2-yl}methyl)-N-propyl-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-({5-[(3R)-3-(Dimethylamino)-1-pyrrolidinyl]imidazo[1,2-a]pyridin-2-yl}methyl)-N-(1-methyl ethyl)-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-(Cyclopropyl methyl)-N-({5-[(3R)-3-(dimethylamino)-1-pyrrolidinyl]imidazo[1,2-a]pyridin-2-yl}methyl)-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-Methyl-N-{1-[5-(4-methyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]ethyl}-5,6,7,8-tetrahydro-8-quinolinamine; and pharmaceutically acceptable salts or esters thereof.
40 . A compound selected from the group consisting of
(8S)—N-Methyl-N-{[5-(4-methyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-{[5-(4-Methyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-N-(2-methylpropyl)-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-Ethyl-N-{[5-(4-methyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-(1-Methylethyl)-N-{[5-(4-methyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-{[5-(4-Methyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-N-propyl-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-(Cyclopropylmethyl)-N-{[5-(4-methyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-Butyl-N-{[5-(4-methyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-5,6,7,8-tetrahydro-8-quinolinamine; 2-{{[5-(4-Methyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}[(8S)-5,6,7,8-tetrahydro-8-quinolinyl]amino}ethanol; 3-{{[5-(4-M ethyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}[(8S)-5,6,7,8-tetrahydro-8-quinolinyl]amino}-1-propanol; (8S)—N-{[5-(4-Amino-1-piperidinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-N-methyl-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-{[5-(Hexahydropyrrolo[1,2-a]pyrazin-2(1H)-yl)imidazo[1,2-a]pyridin-2-yl]methyl}-N-methyl-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-({5-[(3R)-3-(Dimethylamino)-1-pyrrolidinyl]imidazo[1,2-a]pyridin-2-yl}methyl)-N-methyl-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-{[5-(Hexahydro-1H-1,4-diazepin-1-yl)imidazo[1,2-a]pyridin-2-yl]methyl}-N-methyl-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-Methyl-N-{[5-(4-methylhexahydro-1H-1,4-diazepin-1-yl)imidazo[1,2-a]pyridin-2-yl]methyl}-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-Methyl-N-({5-[methyl(1-methyl-3-pyrrolidinyl)amino]imidazo[1,2-a]pyridin-2-yl}methyl)-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-{[5-(4-Ethyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-N-methyl-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-Methyl-N-({5-[4-(1-methylethyl)-1-piperazinyl]imidazo[1,2-a]pyridin-2-yl}methyl)-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-({5-[(3R)-3-Amino-1-pyrrolidinyl]imidazo[1,2-a]pyridin-2-yl}methyl)-N-methyl-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-({5-[(3R)-3-(Diethylamino)-1-pyrrolidinyl]imidazo[1,2-a]pyridin-2-yl}methyl)-N-methyl-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-({5-[(3R)-3-(Dimethylamino)-1-pyrrolidinyl]imidazo[1,2-a]pyridin-2-yl}methyl)-N-ethyl-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-({5-[(3R)-3-(Dimethylamino)-1-pyrrolidinyl]imidazo[1,2-a]pyridin-2-yl}methyl)-N-propyl-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-({5-[(3R)-3-(Dimethylamino)-1-pyrrolidinyl]imidazo[1,2-a]pyridin-2-yl}methyl)-N-(1-methylethyl)-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-(Cyclopropylmethyl)-N-({5-[(3R)-3-(dimethylamino)-1-pyrrolidinyl]imidazo[1,2-a]pyridin-2-yl}methyl)-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-Methyl-N-{1-[5-(4-methyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]ethyl}-5,6,7,8-tetrahydro-8-quinolinamine; and pharmaceutically acceptable salts or esters thereof.
41 . A compound selected from the group consisting of:
(8S)—N-Methyl-N-{[5-(4-methyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-{[5-(4-Methyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-N-(2-methylpropyl)-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-Ethyl-N-{[5-(4-methyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-(1-Methylethyl)-N-{[5-(4-methyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-{[5-(4-Methyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-N-propyl-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-(Cyclopropyl methyl)-N-{[5-(4-methyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-Butyl-N-{[5-(4-methyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-{[5-(4-Ethyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]methyl}-N-methyl-5,6,7,8-tetrahydro-8-quinolinamine; (8S)—N-Methyl-N-{1-[5-(4-methyl-1-piperazinyl)imidazo[1,2-a]pyridin-2-yl]ethyl}-5,6,7,8-tetrahydro-8-quinolinamine; and pharmaceutically acceptable salts or esters thereof.
42 . (canceled)
43 . A pharmaceutical composition comprising a compound according to claim 1 , and a pharmaceutically acceptable carrier.
44 . A composition according to claim 43 , wherein said composition comprises at least one additional therapeutic agent selected from the group consisting of nucleotide reverse transcriptase inhibitors; non-nucleotide reverse transcriptase inhibitors; protease inhibitors; entry inhibitors; Integrase inhibitors; budding inhibitors other CXCR4 and CCR5 inhibitors.
45 . A compound according to claim 1 for use as an active therapeutic substance.
46 . A compound according to claim 1 for use in the treatment or prophylaxis of diseases and conditions caused by inappropriate activity of CXCR4.
47 . A compound according to claim 1 for use in the treatment or prophylaxis of HIV infection, diseases associated with hematopoiesis, controlling the side effects of chemotherapy, enhancing the success of bone marrow transplantation, enhancing wound healing and burn treatment, combating bacterial infections in leukemia, inflammation, inflammatory or allergic diseases, asthma, allergic rhinitis, hypersensitivity lung diseases, hypersensitivity pneumonitis, eosinophilic pneumonitis, delayed-type hypersensitivity, interstitial lung disease (ILD), idiopathic pulmonary fibrosis, systemic lupus erythematosus, ankylosing spondylitis, systemic sclerosis, Sjogren's syndrome, polymyositis or dermatomyositis, systemic anaphylaxis or hypersensitivity responses, drug allergies, insect sting allergies, autoimmune diseases, rheumatoid arthritis, psoriatic arthritis, systemic lupus erythematosus, myastenia gravis, juvenile onset diabetes, glomerulonephritis, autoimmune throiditis, graft rejection, allograft rejection, graft-versus-host disease, inflammatory bowel diseases, Crohn's disease, ulcerative colitus, spondylo-arthropathies, scleroderma, psoriasis, T-cell-mediated psoriasis, inflammatory dermatoses, dermatitis, eczema, atopic dermatitis, allergic contact dermatitis, urticaria, vasculitis, necrotizing, cutaneous, hypersensitivity vasculitis, eoosinophilic myotis, eosinophilic fasciitis, and brain, breast, prostate, lung, or haematopoetic tissue cancers.
48 . The compound of claim 47 wherein the condition or disease is HIV infection, rheumatoid arthritis, inflammation, or cancer.
49 . The compound of claim 47 wherein the condition or disease is HIV infection.
50 . Use of a compound according to claim 1 in the manufacture of a medicament for use in the treatment or prophylaxis of a condition or disease modulated by a chemokine receptor.
51 . Use of a compound according to claim 50 wherein the chemokine receptor is CXCR4.
52 . Use of a compound according to claim 1 in the manufacture of a medicament for use in the treatment or prophylaxis of HIV infection, diseases associated with hematopoiesis, controlling the side effects of chemotherapy, enhancing the success of bone marrow transplantation, enhancing wound healing and burn treatment, combating bacterial infections in leukemia, inflammation, inflammatory or allergic diseases, asthma, allergic rhinitis, hypersensitivity lung diseases, hypersensitivity pneumonitis, eosinophilic pneumonitis, delayed-type hypersensitivity, interstitial lung disease (ILD), idiopathic pulmonary fibrosis, systemic lupus erythematosus, ankylosing spondylitis, systemic sclerosis, Sjogren's syndrome, polymyositis or dermatomyositis, systemic anaphylaxis or hypersensitivity responses, drug allergies, insect sting allergies, autoimmune diseases, rheumatoid arthritis, psoriatic arthritis, systemic lupus erythematosus, myastenia gravis, juvenile onset diabetes, glomerulonephritis, autoimmune throiditis, graft rejection, allograft rejection, graft-versus-host disease, inflammatory bowel diseases, Crohn's disease, ulcerative colitus, spondylo-arthropathies, scleroderma, psoriasis, T-cell-mediated psoriasis, inflammatory dermatoses, dermatitis, eczema, atopic dermatitis, allergic contact dermatitis, urticaria, vasculitis, necrotizing, cutaneous, hypersensitivity vasculitis, eoosinophilic myotis, eosinophilic fasciitis, and brain, breast, prostate, lung, or haematopoetic tissue cancers.
53 . Use of a compound as in claim 52 wherein the condition or disorder is HIV infection, rheumatoid arthritis, inflammation, or cancer.
54 . Use of a compound as in claim 52 wherein the condition or disorder is HIV infection.
55 . A method for the treatment or prophylaxis of a condition or disease modulated by a chemokine receptor comprising the administration of a compound of claim 1 .
56 . The method of claim 55 wherein the chemokine receptor is CXCR4.
57 . A method for the treatment or prophylaxis of HIV infection, diseases associated with hematopoiesis, controlling the side effects of chemotherapy, enhancing the success of bone marrow transplantation, enhancing wound healing and burn treatment, combating bacterial infections in leukemia, inflammation, inflammatory or allergic diseases, asthma, allergic rhinitis, hypersensitivity lung diseases, hypersensitivity pneumonitis, eosinophilic pneumonitis, delayed-type hypersensitivity, interstitial lung disease (ILD), idiopathic pulmonary fibrosis, systemic lupus erythematosus, ankylosing spondylitis, systemic sclerosis, Sjogren's syndrome, polymyositis or dermatomyositis, systemic anaphylaxis or hypersensitivity responses, drug allergies, insect sting allergies, autoimmune diseases, rheumatoid arthritis, psoriatic arthritis, systemic lupus erythematosus, myastenia gravis, juvenile onset diabetes, glomerulonephritis, autoimmune throiditis, graft rejection, allograft rejection, graft-versus-host disease, inflammatory bowel diseases, Crohn's disease, ulcerative colitus, spondylo-arthropathies, scleroderma, psoriasis, T-cell-mediated psoriasis, inflammatory dermatoses, dermatitis, eczema, atopic dermatitis, allergic contact dermatitis, urticaria, vasculitis, necrotizing, cutaneous, hypersensitivity vasculitis, eoosinophilic myotis, eosinophilic fasciitis, and brain, breast, prostate, lung, or haematopoetic tissue cancers comprising the administration of a compound according to claim 1 .
58 . A method for the treatment or prophylaxis of HIV infection, rheumatoid arthritis, inflammation, or cancer comprising the administration of a compound according to claim 1 .
59 . A method for the treatment or prophylaxis of HIV infection comprising the administration of a compound according to claim 1 .
60 . A method of treatment or prevention of a viral infection in a human comprising administering to said human a composition comprising a compound according to claim 1 and another therapeutic agent.
61 . A method according to claim 60 , wherein said therapeutic agent is selected from the group consisting of nucleotide reverse transcriptase inhibitors; non-nucleotide reverse transcriptase inhibitors; protease inhibitors; entry inhibitors; Integrase inhibitors; budding inhibitors; CXCR4 inhibitors; and CCR5 inhibitors.
62 . A process for the preparation of a compound of formula (I)
wherein:
t is 1
each R independently is H;
each R 1 independently is halogen, haloalkyl, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, -Ay, —NHAy, -Het, —NHHet, —OR 10 , —OAy, —OHet, —R a OR 10 , —NR 6 R 7 , —R a NR 6 R 7 , —R a C(O)R 10 , —C(O)R 10 , —CO 2 R 10 , —R a CO 2 R 10 , —C(O)NR 6 R 7 , —C(O)Ay, —C(O)Het, —S(O) 2 NR 6 R 7 , —S(O) q R 10 , —S(O) q Ay, cyano, nitro, or azido;
n is 0, 1, or 2;
R 2 is selected from a group consisting of H, alkyl, haloalkyl, cycloalkyl, —R a cycloalkyl alkenyl, alkynyl, —R a Ay, —R a OR 5 , or —R a S(O) q R 5 ; wherein R 2 is not substituted with amine or alkylamine
R 3 is H, alkyl, haloalkyl, cycloalkyl, alkenyl, alkynyl, —R a Ay, or —R a S(O) q R 5 ; each R 4 independently is halogen, haloalkyl, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, -Ay, —NHAy, -Het, —NHHet, —OR 10 , —OAy, —OHet, —R a OR 10 , —NR 6 R 7 , —R a NR 6 R 7 , —R a C(O)R 10 , —C(O)R 10 , —CO 2 R 10 , —R a CO 2 R 10 , —C(O)NR 6 R 7 , —C(O)Ay, —C(O)Het, —S(O) 2 NR 6 R 7 , —S(O) q R 10 , —S(O) q Ay, cyano, nitro, or azido;
m is 0, 1, or 2;
each R 5 independently is H, alkyl, alkenyl, alkynyl, cycloalkyl, or -Ay;
p is 0 or 1;
Y is —NR 10 —, —O—, —C(O)NR 10 —, —NR 10 C(O)—, —C(O)—, —C(O)O—, —NR 10 C(O)N(R 10 ) 2 —, —S(O) q —, —S(O) q NR 10 —, or —NR 10 S(O) q —;
X is —N(R 10 ) 2 , —R a N(R 10 ) 2 , -AyN(R 10 ) 2 , —R a AyN(R 10 ) 2 , -AyR a N(R 10 ) 2 , —R a AyR a N(R 10 ) 2 , -Het, —R a Het, -HetN(R 10 ) 2 , —R a HetN(R 10 ) 2 , -HetR a N(R 10 ) 2 , —R a HetR a N(R 10 ) 2 , -HetR a Ay, or -HetR a Het;
each R a independently is alkylene optionally substituted with one or more of alkyl, oxo or hydroxyl, cycloalkylene optionally substituted with one or more of alkyl, oxo or hydroxyl, alkenylene, cycloalkenylene, or alkynylene;
each R 10 independently is H, alkyl, cycloalkyl, alkenyl, alkynyl, cycloalkenyl, —R a cycloalkyl, —R a OH, —R a OR 5 , —R a NR 6 R 7 , or —R a Het
each of R 6 and R 7 independently are selected from H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, —R a cycloalkyl, —R a OH, —R a OR 5 , —R a NR 8 R 9 , -Ay, -Het, —R a Ay, —R a Het, or —S(O) q R 5 ;
each of R 8 and R 9 independently are selected from H or alkyl;
each q independently is 0, 1, or 2;
each Ay independently represents an optionally substituted aryl group; and
each Het independently represents an optionally substituted 4-, 5-, or 6-membered heterocyclyl or heteroaryl group;
comprising the steps of reacting a compound of formula (II)
with a compound of formula (IV)
under reductive amination conditions to produce a compound of formula (I).
63 . A process for the preparation of a compound of formula (I)
wherein:
t is 1
each R independently is H;
each R 1 independently is halogen, haloalkyl, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, -Ay, —NHAy, -Het, —NHHet, —OR 10 , —OAy, —OHet, —R a OR 10 , —NR 6 R 7 , —R a NR 6 R 7 , —R a C(O)R 10 , —C(O)R 10 , —CO 2 R 10 , —R a CO 2 R 10 , —C(O)NR 6 R 7 , —C(O)Ay, —C(O)Het, —S(O) 2 NR 6 R 7 , —S(O) q R 10 , —S(O) q Ay, cyano, nitro, or azido;
n is 0, 1, or 2;
R 2 is selected from a group consisting of H, alkyl, haloalkyl, cycloalkyl, —R a cycloalkyl alkenyl, alkynyl, —R a Ay, —R a OR 5 , or —R a S(O) q R 5 ; wherein R 2 is not substituted with amine or alkylamine
R 3 is H, alkyl, haloalkyl, cycloalkyl, alkenyl, alkynyl, —R a Ay, or —R a S(O) q R 5 ; each R 4 independently is halogen, haloalkyl, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, -Ay, —NHAy, -Het, —NHHet, —OR 10 , —OAy, —OHet, —R a OR 10 , —NR 6 R 7 , —R a NR 6 R 7 , —R a C(O)R 10 , —C(O)R 10 , —CO 2 R 10 , —R a CO 2 R 10 , —C(O)NR 6 R 7 , —C(O)Ay, —C(O)Het, —S(O) 2 NR 6 R 7 , —S(O) q R 10 , —S(O) q Ay, cyano, nitro, or azido;
m is 0, 1, or 2;
each R 5 independently is H, alkyl, alkenyl, alkynyl, cycloalkyl, or -Ay;
p is 0 or 1;
Y is —NR 10 —, —O—, —C(O)NR 10 —, —NR 10 C(O)—, —C(O)—, —C(O)O—, —NR 10 C(O)N(R 10 ) 2 —, —S(O) q —, —S(O) q NR 10 —, or —NR 10 S(O) q —;
X is —N(R 10 ) 2 , —R a N(R 10 ) 2 , -AyN(R 10 ) 2 , —R a AyN(R 10 ) 2 , -AyR a N(R 10 ) 2 , —R a AyR a N(R 10 ) 2 , -Het, —R a Het, -HetN(R 10 ) 2 , —R a HetN(R 10 ) 2 , -HetR a N(R 10 ) 2 , —R a HetR a N(R 10 ) 2 , -HetR a Ay, or -HetR a Het;
each R a independently is alkylene optionally substituted with one or more of alkyl, oxo or hydroxyl, cycloalkylene optionally substituted with one or more of alkyl, oxo or hydroxyl, alkenylene, cycloalkenylene, or alkynylene;
each R 10 independently is H, alkyl, cycloalkyl, alkenyl, alkynyl, cycloalkenyl, —R a cycloalkyl, —R a OH, —R a OR 5 , —R a NR 6 R 7 or —R a Het
each of R 6 and R 7 independently are selected from H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, —R a cycloalkyl, —R a OH, —R a OR 5 , —R a NR 8 R 9 , -Ay, -Het, —R a Ay, —R a Het, or —S(O) q R 5 ;
each of R 8 and R 9 independently are selected from H or alkyl;
each q independently is 0, 1, or 2;
each Ay independently represents an optionally substituted aryl group; and
each Het independently represents an optionally substituted 4-, 5-, or 6-membered heterocyclyl or heteroaryl group;
comprising the steps of reacting a compound of formula (III)
wherein R 1 , R 2 and n are as defined with respect to formula (I), with a compound of formula (V)
under reductive amination conditions to produce a compound of formula (I).
64 . A process for the preparation of a compound of formula (I)
wherein:
t is 1
each R independently is H;
each R 1 independently is halogen, haloalkyl, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, -Ay, —NHAy, -Het, —NHHet, —OR 10 , —OAy, —OHet, —R a OR 10 , —NR 6 R 7 , —R a NR 6 R 7 , —R a C(O)R 10 , —C(O)R 10 , —CO 2 R 10 , —R a CO 2 R 10 , —C(O)NR 6 R 7 , —C(O)Ay, —C(O)Het, —S(O) 2 NR 6 R 7 , —S(O) q R 10 , —S(O) q Ay, cyano, nitro, or azido;
n is 0, 1, or 2;
R 2 is selected from a group consisting of H, alkyl, haloalkyl, cycloalkyl, —R a cycloalkyl, alkenyl, alkynyl, —R a Ay, —R a OR 5 , or —R a S(O) q R 5 ; wherein R 2 is not substituted with amine or alkylamine
R 3 is H, alkyl, haloalkyl, cycloalkyl, alkenyl, alkynyl, —R a Ay, or —R a S(O) q R 5 ; each R 4 independently is halogen, haloalkyl, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, -Ay, —NHAy, -Het, —NHHet, —OR 10 , —OAy, —OHet, —R a OR 10 , —NR 6 R 7 , —R a NR 6 R 7 , —R a C(O)R 10 , —C(O)R 10 , —CO 2 R 10 , —R a CO 2 R 10 , —C(O)NR 6 R 7 , —C(O)Ay, —C(O)Het, —S(O) 2 NR 6 R 7 , —S(O) q R 10 , —S(O) q Ay, cyano, nitro, or azido;
m is 0, 1, or 2;
each R 5 independently is H, alkyl, alkenyl, alkynyl, cycloalkyl, or -Ay;
p is 0 or 1;
Y is —NR 10 —, —O—, —C(O)NR 10 —, —NR 10 C(O)—, —C(O)—, —C(O)O—, —NR 10 C(O)N(R 10 ) 2 —, —S(O) q —, —S(O) q NR 10 —, or —NR 10 S(O) q —;
X is —N(R 10 ) 2 , —R a N(R 10 ) 2 , -AyN(R 10 ) 2 , —R a AyN(R 10 ) 2 , -AyR a N(R 10 ) 2 , —R a AyR a N(R 10 ) 2 , -Het, —R a Het, -HetN(R 10 ) 2 , —R a HetN(R 10 ) 2 , -HetR a N(R 10 ) 2 , —R a HetR a N(R 10 ) 2 , -HetR a Ay, or -HetR a Het;
each R a independently is alkylene optionally substituted with one or more of alkyl, oxo or hydroxyl, cycloalkylene optionally substituted with one or more of alkyl, oxo or hydroxyl, alkenylene, cycloalkenylene, or alkynylene;
each R 10 independently is H, alkyl, cycloalkyl, alkenyl, alkynyl, cycloalkenyl, —R a cycloalkyl, —R a OH, —R a OR 5 , —R a NR 6 R 7 , or —R a Het
each of R 6 and R 7 independently are selected from H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, —R a cycloalkyl, —R a OH, —R a OR 5 , —R a NR 8 R 9 , -Ay, -Het, —R a Ay, —R a Het, or —S(O) q R 5 ;
each of R 8 and R 9 independently are selected from H or alkyl;
each q independently is 0, 1, or 2;
each Ay independently represents an optionally substituted aryl group; and
each Het independently represents an optionally substituted 4-, 5-, or 6-membered heterocyclyl or heteroaryl group;
comprising the steps of reacting a compound of formula (III)
wherein R 1 , R 2 , and n are as defined with respect to formula (I), with a compound of formula (VI)
wherein R 3 , R 4 , Y, X, p and m are as defined with respect to formula (I) and LV is a leaving group, to produce a compound of formula (I).
65 . A process for the preparation of a compound of formula (I-A)
wherein:
each R 1 independently is halogen, haloalkyl, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, -Ay, —NHAy, -Het, —NHHet, —OR 10 , —OAy, —OHet, —R a OR 10 , —NR 6 R 7 , —R a NR 6 R 7 , —R a C(O)R 10 , —C(O)R 10 , —CO 2 R 10 , —R a CO 2 R 10 , —C(O)NR 6 R 7 , —C(O)Ay, —C(O)Het, —S(O) 2 NR 6 R 7 , —S(O) q R 10 , —S(O) q Ay, cyano, nitro, or azido;
n is 0, 1, or 2;
R 2 is selected from a group consisting of H, alkyl, haloalkyl, cycloalkyl, —R a cycloalkyl alkenyl, alkynyl, —R a Ay, —R a OR 5 , or —R a S(O) q R 5 ; wherein R 2 is not substituted with amine or alkylamine
R 3 is H, alkyl, haloalkyl, cycloalkyl, alkenyl, alkynyl, —R a Ay, or —R a S(O) q R 5 ;
each R 4 independently is halogen, haloalkyl, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, -Ay, —NHAy, -Het, —NHHet, —OR 10 , —OAy, —OHet, —R a OR 10 , —NR 6 R 7 , —R a NR 6 R 7 , —R a C(O)R 10 , —C(O)R 10 , —CO 2 R 10 , —R a CO 2 R 10 , —C(O)NR 6 R 7 , —C(O)Ay, —C(O)Het, —S(O) 2 NR 6 R 7 , —S(O) q R 10 , —S(O) q Ay, cyano, nitro, or azido;
m is 0, 1, or 2;
each R 5 independently is H, alkyl, alkenyl, alkynyl, cycloalkyl, or -Ay;
p is 0 or 1;
Y is —NR 10 —, —O—, —C(O)NR 10 —, —NR 10 C(O)—, —C(O)—, —C(O)O—, —NR 10 C(O)N(R 10 ) 2 —, —S(O) q —, —S(O) q NR 10 —, or —NR 10 S(O) q —;
X is —N(R 10 ) 2 , —R a N(R 10 ) 2 , -AyN(R 10 ) 2 , —R a AyN(R 10 ) 2 , -AyR a N(R 10 ) 2 , —R a AyR a N(R 10 ) 2 , -Het, —R a Het, -HetN(R 10 ) 2 , —R a HetN(R 10 ) 2 , -HetR a N(R 10 ) 2 , —R a HetR a N(R 10 ) 2 , -HetR a Ay, or -HetR a Het;
each R a independently is alkylene optionally substituted with one or more of alkyl, oxo or hydroxyl, cycloalkylene optionally substituted with one or more of alkyl, oxo or hydroxyl, alkenylene, cycloalkenylene, or alkynylene;
each R 10 independently is H, alkyl, cycloalkyl, alkenyl, alkynyl, cycloalkenyl, —R a cycloalkyl, —R a OH, —R a OR 5 , —R a NR 6 R 7 , or —R a Het;
each of R 6 and R 7 independently are selected from H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, —R a cycloalkyl, —R a OH, —R a OR 5 , —R a NR 8 R 9 , -Ay, -Het, —R a Ay, —R a Het, or —S(O) q R 5 ;
each of R 8 and R 9 independently are selected from H or alkyl;
each q independently is 0, 1, or 2;
each Ay independently represents an optionally substituted aryl group; and
each Het independently represents an optionally substituted 4-, 5-, or 6-membered heterocyclyl or heteroaryl group;
comprising the steps of treating a compound of formula (X)
wherein R 1 , R 2 , R 3 , R 4 , m and n are as defined with respect to formula (I-A), with a nucleophile to produce a compound of formula (I-A).
66 . A process for the preparation of a compound of formula (I-C)
wherein:
each R 1 independently is halogen, haloalkyl, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, -Ay, —NHAy, -Het, —NHHet, —OR 10 , —OAy, —OHet, —R a OR 10 , —NR 6 R 7 , —R a NR 6 R 7 , —R a C(O)R 10 , —C(O)R 10 , —CO 2 R 10 , —R a CO 2 R 10 , —C(O)NR 6 R 7 , —C(O)Ay, —C(O)Het, —S(O) 2 NR 6 R 7 , —S(O) q R 10 , —S(O) q Ay, cyano, nitro, or azido;
n is 0, 1, or 2;
R 2 is selected from a group consisting of H, alkyl, haloalkyl, cycloalkyl, —R a cycloalkyl alkenyl, alkynyl, —R a Ay, —R a OR 5 , or —R a S(O) q R 5 ; wherein R 2 is not substituted with amine or alkylamine
R 3 is H, alkyl, haloalkyl, cycloalkyl, alkenyl, alkynyl, —R a Ay, or —R a S(O) q R 5 ; each R 4 independently is halogen, haloalkyl, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, -Ay, —NHAy, -Het, —NHHet, —OR 10 , —OAy, —OHet, —R a OR 10 , —NR 6 R 7 , —R a NR 6 R 7 , —R a C(O)R 10 , —C(O)R 10 , —CO 2 R 10 , —R a CO 2 R 10 , —C(O)NR 6 R 7 , —C(O)Ay, —C(O)Het, —S(O) 2 NR 6 R 7 , —S(O) q R 10 , —S(O) q Ay, cyano, nitro, or azido;
m is 0, 1, or 2;
each R 5 independently is H, alkyl, alkenyl, alkynyl, cycloalkyl, or -Ay;
each R a independently is alkylene optionally substituted with one or more of alkyl, oxo or hydroxyl, cycloalkylene optionally substituted with one or more of alkyl, oxo or hydroxyl, alkenylene, cycloalkenylene, or alkynylene;
each R 10 independently is H, alkyl, cycloalkyl, alkenyl, alkynyl, cycloalkenyl, —R a cycloalkyl, —R a OH, —R a OR 5 , —R a NR 6 R 7 , or —R a Het
each of R 6 and R 7 independently are selected from H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, —R a cycloalkyl, —R a OH, —R a OR 5 , —R a NR 8 R 9 , -Ay, -Het, —R a Ay —R a Het, or —S(O) q R 5 ;
each of R 8 and R 9 independently are selected from H or alkyl;
each q independently is 0, 1, or 2;
each Ay independently represents an optionally substituted aryl group; and
each Het independently represents an optionally substituted 4-, 5-, or 6-membered heterocyclyl or heteroaryl group;
comprising the steps of reacting a compound of formula (X)
wherein R 1 , R 2 , R 3 , R 4 , n and m are as defined with respect to formula (I-C), with a compound of formula (XIII)
in the presence of a catalyst to form a compound of formula (XII)
wherein R 1 , R 2 , R 3 , n and m are as defined with respect to formula (I-C) and reducing the compound of formula (XII) to produce a compound of formula (I-C).
67 . A process for the preparation of a compound of formula (I-D)
wherein:
each R 1 independently is halogen, haloalkyl, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, -Ay, —NHAy, -Het, —NHHet, —OR 10 , —OAy, —OHet, —R a OR 10 , —NR 6 R 7 , —R a NR 6 R 7 , —R a C(O)R 10 , —C(O)R 10 , —CO 2 R 10 , —R a CO 2 R 10 , —C(O)NR 6 R 7 , —C(O)Ay, —C(O)Het, —S(O) 2 NR 6 R 7 , —S(O) q R 10 , —S(O) q Ay, cyano, nitro, or azido;
n is 0, 1, or 2;
R 2 is selected from a group consisting of H, alkyl, haloalkyl, cycloalkyl, —R a cycloalkyl, alkenyl, alkynyl, —R a Ay, —R a OR 5 , or —R a S(O) q R 5 ; wherein R 2 is not substituted with amine or alkylamine
R 3 is H, alkyl, haloalkyl, cycloalkyl, alkenyl, alkynyl, —R a Ay, or —R a S(O) q R 5 ; each R 4 independently is halogen, haloalkyl, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, -Ay, —NHAy, -Het, —NHHet, —OR 10 , —OAy, —OHet, —R a OR 10 , —NR 6 R 7 , —R a NR 6 R 7 , —R a C(O)R 10 , —C(O)R 10 , —CO 2 R 10 , —R a CO 2 R 10 , —C(O)NR 6 R 7 , —C(O)Ay, —C(O)Het, —S(O) 2 NR 6 R 7 , —S(O) q R 10 , —S(O) q Ay, cyano, nitro, or azido;
m is 0, 1, or 2;
each R 5 independently is H, alkyl, alkenyl, alkynyl, cycloalkyl, or -Ay;
p is 1;
Y is —C(O)NR 10 —;
X is —N(R 10 ) 2 , —R a N(R 10 ) 2 , -AyN(R 10 ) 2 , —R a AyN(R 10 ) 2 , -AyR a N(R 10 ) 2 , —R a AyR a N(R 10 ) 2 , -Het, —R a Het, -HetN(R 10 ) 2 , —R a HetN(R 10 ) 2 , -HetR a N(R 10 ) 2 , —R a HetR a N(R 10 ) 2 , -HetR a Ay, or -HetR a Het;
each R a independently is alkylene optionally substituted with one or more of alkyl, oxo or hydroxyl, cycloalkylene optionally substituted with one or more of alkyl, oxo or hydroxyl, alkenylene, cycloalkenylene, or alkynylene;
each R 10 independently is H, alkyl, cycloalkyl, alkenyl, alkynyl, cycloalkenyl, —R a cycloalkyl, —R a OH, —R a OR 5 , —R a NR 6 R 7 , or —R a Het;
each of R 6 and R 7 independently are selected from H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, —R a cycloalkyl, —R a OH, —R a OR 5 , —R a NR 8 R 9 , -Ay, -Het, —R a Ay, —R a Het, or —S(O) q R 5 ;
each of R 8 and R 9 independently are selected from H or alkyl;
each q independently is 0, 1, or 2;
each Ay independently represents an optionally substituted aryl group; and
each Het independently represents an optionally substituted 4-, 5-, or 6-membered heterocyclyl or heteroaryl group;
comprising the steps of deprotecting a compound of formula (XVI)
wherein R 1 , R 2 , R 3 , R 4 , n, and m is as defined with respect to formula (I-D), to form a carboxylic acid type compound and subsequently coupling the carboxylic acid type compound with an amine to form a compound of formula (I-D).
68 . A process for the preparation of a compound of formula (I-E)
wherein:
each R 1 independently is halogen, haloalkyl, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, -Ay, —NHAy, -Het, —NHHet, —OR 10 , —OAy, —OHet, —R a OR 10 , —NR 6 R 7 , —R a NR 6 R 7 , —R a C(O)R 10 , —C(O)R 10 , —CO 2 R 10 , —R a CO 2 R 10 , —C(O)NR 6 R 7 , —C(O)Ay, —C(O)Het, —S(O) 2 NR 6 R 7 , —S(O) q R 10 , —S(O) q Ay, cyano, nitro, or azido;
n is 0, 1, or 2;
R is selected from a group consisting of H, alkyl, haloalkyl, cycloalkyl, —R a cycloalkyl, alkenyl, alkynyl, —R a Ay, —R a OR 5 , or R a S(O) q R 5 ; wherein R 2 is not substituted with amine or alkylamine;
R 3 is H, alkyl, haloalkyl, cycloalkyl, alkenyl, alkynyl, —R a Ay, or —R a S(O) q R 5 ; each R 4 independently is halogen, haloalkyl, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, -Ay, —NHAy, -Het, —NHHet, —OR 10 , —OAy, —OHet, —R a OR 10 , —NR 6 R 7 , —R a NR 6 R 7 , —R a C(O)R 10 , —C(O)R 10 , —CO 2 R 10 , —R a CO 2 R 10 , —C(O)NR 6 R 7 , —C(O)Ay, —C(O)Het, —S(O) 2 NR 6 R 7 , —S(O) q R 10 , —S(O) q Ay, cyano, nitro, or azido;
m is 0, 1, or 2;
each R 5 independently is H, alkyl, alkenyl, alkynyl, cycloalkyl, or -Ay;
p is 1;
Y is —NR 10 C(O)—;
X is —N(R 10 ) 2 , —R a N(R 10 ) 2 , -AyN(R 10 ) 2 , —R a AyN(R 10 ) 2 , -AyR a N(R 10 ) 2 , —R a AyR a N(R 10 ) 2 , -Het, —R a Het, -HetN(R 10 ) 2 , —R a HetN(R 10 ) 2 , -HetR a N(R 10 ) 2 , —R a HetR a N(R 10 ) 2 , -HetR a Ay, or -HetR a Het;
each R a independently is alkylene optionally substituted with one or more of alkyl, oxo or hydroxyl, cycloalkylene optionally substituted with one or more of alkyl, oxo or hydroxyl, alkenylene, cycloalkenylene, or alkynylene;
each R 10 independently is H, alkyl, cycloalkyl, alkenyl, alkynyl, cycloalkenyl, —R a cycloalkyl, —R a OH, —R a OR 5 , —R a NR 6 R 7 , or —R a Het;
each of R 6 and R 7 independently are selected from H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, —R a cycloalkyl, —R a OH, —R a OR 5 , —R a NR 8 R 9 , -Ay, -Het, —R a Ay, —R a Het, or —S(O) q R 5 ;
each of R 8 and R 9 independently are selected from H or alkyl;
each q independently is 0, 1, or 2;
each Ay independently represents an optionally substituted aryl group; and
each Het independently represents an optionally substituted 4-, 5-, or 6-membered heterocyclyl or heteroaryl group;
comprising the steps of coupling an amine of formula (XXII)
wherein R 1 , R 2 , R 3 , R 4 , n and m are as defined with respect to formula (I-E) with a carboxylic acid derivative to form a compound of formula (I-E).
69 . A process for the preparation of a compound of formula (XXXI)
wherein Z is C 1 -C 6 alkyl or C 3 -C 8 cycloalkyl, comprising the steps of reacting a compound of formula (XXIX)
wherein Z is C 1 -C 6 alkyl or C 3 -C 8 cycloalkyl, with a compound of formula (XXX)
under reductive amination conditions to produce a compound of formula (XXXI).
70 . A process for the preparation of a compound of formula (I-F)
wherein Z is C 1 -C 6 alkyl or C 3 -C 8 cycloalkyl, comprising the steps of removing a 4-(methyloxyphenyl)ethyl group from a compound of formula (XXXI)
wherein Z is C 1 -C 6 alkyl or C 3 -G 8 cycloalkyl, followed by reductive amination with an aldehyde to produce a compound of formula (I-F).Join the waitlist — get patent alerts
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